Collado-Hidalgo Alicia, Bower Julienne E, Ganz Patricia A, Irwin Michael R, Cole Steve W
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience and Human Behavior, USA.
Brain Behav Immun. 2008 Nov;22(8):1197-200. doi: 10.1016/j.bbi.2008.05.009. Epub 2008 Jul 9.
Converging evidence from basic and clinical studies suggests a role for proinflammatory cytokines in cancer-related fatigue, although the etiology of elevated inflammatory processes is unclear. We examined single nucleotide polymorphisms (SNPs) in the promoters of cytokine genes as genetic risk factors for cytokine-related fatigue in 33 fatigued and 14 non-fatigued breast cancer survivors, focusing on promoter sequence polymorphisms in IL1B and IL6 associated with differential expression of proinflammatory cytokines. Predictors of fatigue included presence of at least one cytosine at IL1B -511 (95%CI=0.91-16.6, p=.007) and homozygosity for either variant of the IL6 -174 genotype (G/G or C/C; 95%CI=1.12-17.9, p=.027). Associations between fatigue status and IL1B genotype remained significant after covariate adjustment for demographic, biobehavioral and treatment-related factors. These findings provide preliminary evidence that polymorphisms in IL1B may serve as a potential risk factor for persistent fatigue in the aftermath of cancer.
基础研究和临床研究的越来越多的证据表明，促炎细胞因子在癌症相关疲劳中发挥作用，尽管炎症过程加剧的病因尚不清楚。我们在33名疲劳的和14名未疲劳的乳腺癌幸存者中，研究了细胞因子基因启动子中的单核苷酸多态性（SNP）作为细胞因子相关疲劳的遗传风险因素，重点关注与促炎细胞因子差异表达相关的IL1B和IL6启动子序列多态性。疲劳的预测因素包括IL1B -511处至少有一个胞嘧啶（95%CI=0.91-16.6，p=0.007）以及IL6 -174基因型的任一变异的纯合性（G/G或C/C；95%CI=1.12-17.9，p=0.027）。在对人口统计学、生物行为和治疗相关因素进行协变量调整后，疲劳状态与IL1B基因型之间的关联仍然显著。这些发现提供了初步证据，表明IL1B中的多态性可能是癌症后持续性疲劳的潜在风险因素。
